1. Field of the Invention
The recent discovery of retroviruses capable of infecting human lymphocytes, particularly T-cells, resulting in their transformation to lymphomas and leukemias offers insight into the etiology of these types of tumors. For the most part, transforming retroviral viruses observed with mammals other than humans had been divided into two groups: chronic transforming viruses, which integrate into the genome and are thought to lead to transformation by insertional mutagenesis, with activation of a cellular gene; and acutely transforming retroviruses which carry specific transforming sequences (viral oncogenes) which are related to cellular oncogenes or proto-oncogenes (Hayward et al., Nature (1981) 290:475; Nusse et al., Nature (1984) 307:131; Payne et al., Nature (1982) 295:209). However, the more recently discovered family of human T-lymphotropic viruses known as HTLV appear neither to integrate at specific sites nor have a viral oncogene with a normal cellular homolog. The mechanism of transformation by viruses in the HTLV family therefore appears to be different from other known retroviruses. The mechanism of action of viruses in the HTLV family is of interest since HTLV's have been connected with several devastating diseases. In particular, HTLV-I is associated with adult T-cell leukemia and HTLV-II has been isolated from a T-cell variant of hairy cell leukemia.
In order to be able to understand the mechanism of transformation or infection by viruses in the HTLV family to allow for diagnosis, therapy, and in vitro applications which allow for controlled transformation or infection of T-cells, it is of interest to determine the mechanism by which the viruses in the HTLV family transform or infect T-cells or other immune cells and then characterize and isolate compositions involved in the transformation or infection, as well as proliferation and growth cycle of the viruses.
2. Description of the Prior Art
The nucleotide sequences of HTLV-I and -II demonstrate a highly conserved region located between env and the 3' LTR of the virus, which finds its only analogy in a homologous sequence in bovine leukemia virus (Haseltine et al., Science (1984) 225:419). Seiki et al., Proc. Natl. Acad. Sci. USA (1983) 80:3618-3622, have reported four open reading frames in the X sequence of HTLV-I. Haseltine et al., Science (1984) 225:419, as well as Shimotohno et al., Proc. Natl. Acad. Sci. USA (1984) 81:1079-1083, report that there are three open reading frames in a region referred to as the X sequence of HTLV-II. Comparison of the nucleotide sequences of the X regions from the two viruses reveals significant sequence homology (about 75%) between the pX-IV region of HTLV-I and the pX-c region of HTLV-II. More recent data has shown that the amount of homology at the nucleotide level is minimal between the genome of HTLV-III and the genomes of the other viruses in the HTLV series.